The Impact of Mutations

Part 1: A Belgian Blue Mound of Beef

The Belgian Blue is a breed of cattle that is, well, pretty dang buff. They are extremely muscular. At two years of age, males can weigh over 1700 pounds, and females over 1100 pounds! This breed originated in the 1850’s in Belgium as a result of breeding two different types of cattle. One questions biologists have obviously asked is, what causes these cattle to develop such a herculean physique? Is it their diet, a regimen of high weight, low rep training regimen, or something in their DNA? We are going to look at some evidence that suggest that the secret actually lies in their DNA.

The Belgian Blue flexing for the camera… terrifying.

Myostatin(Which is also called growth and differentiation factor-8) is a protein found in the skeletal muscle of mammals. It is a growth factor- a molecule that plays a part in controlling cell division, cell growth, and cell development. Experimenters at Johns Hopkins University discovered the role of the gene first in, what else, mice. Mice were genetically engineered to have their myostatin gene “knocked out” (which means they silenced it so it wasn’t expressed). The resulting mice developed two to three times more muscle than mice with a normal version of the gene. The experimenters described the mice, and I’m not kidding here, as looking “like Schwartzenegger mice”. Analysis of the muscle tissue of the mice showed that the number of muscle cells and size of muscle cells in the issue were two to three times greater in the muscle tissue of the knockout mice than in normal mice.

Mutations Notes

Mutations are ______in the genetic material of the cell. ______are alterations of just ______nucleotide base of a gene. They come in two variations:

  1. Nucleotide-pair substitutions:
  • Missense mutations –
  • Nonsense mutations –
  • Silent mutations –
  1. Insertions and Deletions:
  • Have a ______effect on protein more often than substitutions. Why?
  • Frameshift mutations –

Mutagens –

Pre-Activity Questions:

1)Where is myostatin found?

2)What is a growth factor?

3)What is meant by the term “knockout mice”?

4)What type of mutations would have no effect on an individual?

5)Which type of mutation will probably have the most serious effect on an individual? Why?

Part 1 Procedure:

  1. Using the DNA sequence for normal myostatin below, determine the amino acid sequence for normal myostatin. ** NOTE** YOU ARE ONLY TRANSCRIBING AND TRANSLATING A SMALL PORTION OF THE DNA SEQUENCE FOR THIS PROTEIN. YOU HAVE THE DNA SEQUENCE FOR AMINO ACIDS 273 – 288 OUT OF A TOTAL OF 376 AMINO ACIDS IN THE PROTEIN.
  1. Using the DNA sequence for Belgian Blue myostatin below, determine the amino acid sequence for Belgian Blue myostatin. Again, you only have a small portion of the DNA sequence for the Belgian Blue myostatin, beginning with the triplet codon for amino acid number 273.
  1. Using an arrow, point out where the mutation in the DNA sequence for Belgian Blue myostatin is located.

Post-Activity Questions:

1)Based on the appearance of the organisms that have a mutated version of the myostatin gene, what does the function of myostatin seem to be in mammals?

2)What type of mutation occurred in the Belgian Blue myostatin?

3)How many bases were changed, inserted, or deleted in the Belgian Blue myostatin?

4)What was the result of the mutation that occurred? i.e. Was is a silent mutation, missense, nonsense?

5)A breed of cattle called the Piedmontese cattle has the same type of extra muscle as the Belgian Blue cattle; however, the mutation to the myostatin gene is different. It is caused by a point mutation that change a guanine to an adenine at DNA nucleotide number 941. This causes cysteine to be replaced with tyrosine in the amino acid sequence. Is this a silent mutation, missense mutation, or nonsense mutation?

Part 2: Hemoglobin and sickled cells

Hemoglobin is a protein found in the erythrocytes (red blood cells) of mammals. Its function is to carry oxygen from the lungs to all of the cells of the body, and carbon dioxide from all of the cells of the body to the lungs. The protein consists of 574 amino acids that are arranged in to 4 subunits. 2 of the subunits are identical to each other and called alpha-globin subunits. The other 2 subunits are also identical to one another, but are called beta-globin subunits.

Sickle Cell Anemia:

In an individual with sickle cell anemia, the red blood cells, which are responsible for carrying oxygen and carbon dioxide throughout the body, are shaped like the letter “C”. Normal red blood cells, on the other hand, are shaped like a doughnut without a hole in the middle. The reason for the misshapen cell in individuals with sickle cell anemia is the hemoglobin protein in the red blood cells is abnormal. The sickle-shaped red blood cells don’t pass through blood vessels easily, and tend to clump and stick together. This can lead to severe pain, serious infections, and organ damage.

Anemia is having less than the normal number of red blood cells. The red blood cells in individuals with sickle cell anemia only live 10-20 days, whereas a normal red blood cell lives for 120 days.

Pre-Activity Questions:

1)Where is hemoglobin found?

2)What is the role of hemoglobin in the body?

3)Compare the shape of a normal red blood cell to that of a red blood cell in someone with sickle cell anemia.

4)What is anemia, and why do people with sickle cell anemia have anemia?

Part 2 Procedure:

  1. Using the DNA sequence for normal hemoglobin below, determine the amino acid sequence for normal hemoglobin. **NOTE** YOU ARE ONLY TRANSCRIBING AND TRANSLATING A SMALL PORTION OF THE DNA DEQUENCE FOR THE BETA-GLOBIN SUBUNIT OF THE PROTEIN. YOU HAVE THE DNA SEQUENCE FOR AMINO ACIDS 1-7 OUT OF A TOTAL OF 146 AMINO ACIDS IN THE BETA-GLOBIN SUBUNIT.
  1. Using the DNA sequence for sickle cell hemoglobin, determine the amino acid sequence for sickle cell hemoglobin. Again, you only have a small portion of the sequence beginning with the triplet codon for amino acid number 1.
  1. Either circle of highlight where the mutation for sickle-cell hemoglobin is located.

Post-Activity Questions:

1)What type of mutation occurred in the gene for sickle-cell hemoglobin?

2)How many bases were changed, inserted, or deleted in the gene for sickle-cell hemoglobin?

3)What was the result of the mutation that occurred? i.e. Was it a silent, missense, or nonsense mutation?

4)Sickle cell anemia is more common in our modern population than in the past, and individuals with sickle cell anemia are living much longer lives than they used to. Why do you suppose this is the case?

5)In the spaces provided below write a 3-nucleotide DNA sequence, then transcribe and translate it. Then, change one letter in the DNA sequence so that the amino acid does not change.

What type of mutation is this?